Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding.

Abstract

RATIONALE:

Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for the justification of alternative pain therapies.

OBJECTIVE:

This study systematically examined the antihyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen.

METHODS:

Von Frey and Hargreaves tests were used to examine the antihyperalgesic effects of drugs in complete Freund's adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays.

RESULTS:

2-BFI (3.2-17.8 mg/kg, i.p.), phenyzoline (17.8-100 mg/kg, i.p.), and acetaminophen (56-178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner.

CONCLUSIONS:

Quantitative analysis of the antihyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen.

• Authors: Justin N Siemian, Jiuzhou Li, Yanan Zhang, Jun-Xu Li
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 233 Issue 5 Pg. 873-82 (Mar 2016) ISSN: 1432-2072 [Electronic] Germany
• PMID: 26613734 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Benzofurans
• Imidazoles
• Imidazoline Receptors
• Imidazolines
• Ligands
• phenyzoline
• Acetaminophen
• 2-(2-benzofuranyl)-2-imidazoline

Topics

• Acetaminophen (pharmacology)
• Analgesics, Non-Narcotic (pharmacology)
• Animals
• Arthritis, Experimental (psychology)
• Benzofurans (pharmacology)
• Conditioning, Operant (drug effects)
• Dose-Response Relationship, Drug
• Drug Interactions
• Hyperalgesia (drug therapy)
• Imidazoles (pharmacology)
• Imidazoline Receptors (drug effects)
• Imidazolines (pharmacology)
• Ligands
• Male
• Pain (drug therapy, psychology)
• Pain Measurement (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reinforcement Schedule